Infection of L cells by mengovirus or vesicular stomatitis virus (VSV) results in the inhibition of cellular protein synthesis. The mechanism by which this inhibition takes place is not understood. We have evidence in the case of VSV infected cells that suggests that newly synthesized VSV-N protein plays an important role in this process. We wish to verify this observation and to determine the role of the N protein in the inhibition. Experiments are planned to isolate the mRNA for the N protein and add it to a cell-free translation system programmed by cellular mRNA. If N protein is involved in shut off, then translation of the N protein mRNA should lead to cellular protein synthesis inhibition. We are also studying the effect of double infection of HeLa and L cells by VSV and mengovirus on viral mRNA translation. Our results indicate that in VSV infected HeLa cells, superinfection by mengovirus results in the inhibition of translation of VSV proteins. However, in VSV infected L cells, superinfection by mengovirus has no effect on VSV protein synthesis. Both VSV and mengovirus inhibit cellular protein synthesis in both cell types. We are currently in the process of carrying out mixing experiments with lysates from both cells singly or doubly infected with VSV and/or mengovirus in an attempt to understand why in one case (HeLa cell) mengovirus interferes with the translation of VSV mRNA, while in the other case (Lcell), it does not.